OP0221 THERAPY WITH JAK INHIBITORS AND THE RISK OF CARDIOVASCULAR EVENTS IN A DUTCH RHEUMATOID ARTHRITIS POPULATION
Authors: C. Popa, M. Opdam, N. Den Broeder, M. Wientjes, A. Den Broeder
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Most of the disease modifying anti-rheumatic drugs (DMARDs) have cardioprotective potential and using them to achieve remission and/or low disease activity in rheumatoid arthritis (RA) importantly diminishes the cardiovascular risk in these patients. Yet for some of these drugs, including JAK-inhibitors, the modulatory effect on cardiovascular risk seems less straightforward [1]. Caution has been advocated recently when using Janus kinase inhibitors (JAKi) in patients with an unfavorable cardiovascular risk profile [2]. For patients who are about to switch medication the decision of giving JAKi can easily be postponed, however for patients in remission while using JAKi the decision to continue or not is much complex and difficult. Therefore, more research into this issue is warranted in order to better guide clinicians in their daily practice. <h3>Objectives</h3> The aim of this study was to investigate the occurrence of cardiovascular events in a large population of RA patients treated with either JAK-inhibitors or other (b)DMARDs, using real-world data. <h3>Methods</h3> Adult RA patients (extrapolated from drug based algorithms), starting a new bDMARD or JAK-inhibitor between August 1<sup>st</sup> 2017 and January 31<sup>st</sup> 2022, have been selected from IQVIA's Dutch Real-World Data Longitudinal Prescription database, covering about 63% of outpatient prescriptions in the Netherlands. Study outcome is cardiovascular (CV) event defined as the start of platelet aggregation inhibitors (clopidogrel, prasugrel, ticagrelor, dipyridamol) during study period. The risk of cardiovascular events was estimated using multilevel Poisson regression, adjusted for exposition time and confounders. <h3>Results</h3> In total, 15.191 unique patients were included, with 20.912 treatment episodes with either JAKi (2.090, almost exclusively tofacitinib and baricitinib) or bDMARDs (18.822). Most patients were female (72%) and median age was 62 years. We found a total of 681 CV events occurring during the study period: 48 (2.0 events/100 patient years) during therapy with JAKi and 633 (2.42 events/100 patient years) during therapy with bDMARDs, respectively, resulting in an adjusted incidence risk ratio (IRR) of 0.78 for JAKi compared to bDMARDs (95% confidence interval (CI), 0.56 – 1.10) (Table 1). Subanalysis in patients using either tofacitinib or baricitinib yielded similar results (Table 1). Likewise, RA patients older than 65 years did not have a higher risk for CVD during the therapy with JAKi as compared to those treated with bDMARDs: adjusted IRR 0.78 (95% CI, 0.51 – 1.19). <h3>Conclusion</h3> In the Dutch RA population, the incidence of cardiovascular events in JAKi starters was not higher than in bDMARDs starters, and similar for tofacitinib and baricitinib. These data will further contribute to estimation of the cardiovascular safety of JAKi. <h3>References</h3> [1]Atzeni F, Popa CD, et al. Safety of JAK inhibitors: focus on cardiovascular and thromboembolic events. Expert Rev Clin Immunol 2022; 18:233-244. [2]https://www.ema.europa.eu/en/news/ema-recommends-measures-minimise-risk-serious-side-effects-janus-kinase-inhibitors-chronic <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Calin Popa: None declared, Merel Opdam: None declared, Nathan den Broeder: None declared, Maike Wientjes: None declared, Alfons den Broeder Grant/research support from: Grants to the institution from Abbvie, Gilead, Pfizer, Novartis, Lilly, Galapagos, Sanofi.